Tuesday, July 21, 2015

More Harm than Good - The American Pharmaceutical Industry

Updated November 2016

In looking for source material on the state of healthcare in the United States and Canada, I stumbled on this interesting paper written by Donald Light, Joel Lexchin and Jonathan Darrow entitled "Institutional Corruption of Pharmaceuticals and the Myth of Safe and Effective Drugs".

Let's begin by looking at some background information about the drug approval process in the United States.  The Center for Drug Evaluation and Research (or CDER) was created in 1987 as the division within the U.S. Food and Drug Administration (FDA) that is ultimately responsible for determining which prescription, generic and over-the-counter drugs should be approved for public use.  While this seems like a great filter, the funding for CDER does not come from taxpayers, it comes from user fees paid by the same biopharma companies that are seeking approval for their products.  These fees fall under the Prescription Drug User Fee Act (PDUFA) which was passed in 1992.  These user fees allowed the FDA to hire 600 more drug reviewers; in return, companies received a guarantee that the FDA would review priority applications within 6 months and standard applications within 12 months, down from roughly 30 months before the PDUFA was implemented.  At the very least, this has the appearance of a conflict of interest and, as you will see, leads to additional dangerous complications.  The paperwork for new drug approvals in the United States can often exceed 100,000 pages in length, another factor that greatly complicates the approval process.

Now, let's look at some statistics.  A review of the 39 most scientifically sound studies on prescription drugs that were performed between 1964 and 1995 found that 4.7 percent of all hospital admissions were due to serious reactions from prescription drugs that had been appropriately prescribed by physicians and used by patients.  In addition, 2.1 percent of patients in hospitals experienced an adverse drug reaction, resulting in a combined total of 6.8 percent of hospital patients that experienced an adverse drug reaction.  If we multiply this by the 40 million annual admissions to hospitals in the United States, data indicates that at least 2.7 million Americans experience a serious adverse drug reaction annually.  This does not include those who have an adverse reaction at home or in a long-term care facility.  Of all hospitalized patients, 0.32 percent or 128,000 died of complications from prescription drugs annually, matching strokes as the fourth leading cause of death.  If we look at data outside of hospitals, the number of adverse side effects is even worse.  It is estimated that there are 30 adverse reactions occur outside of hospitals for every one that leads to hospitalization, meaning that about 81 million adverse side effects are experienced every year due to prescription medications.  Many of these go unreported.

Let's look at the paper by Light et al.  The authors open with these observations:

"Institutional corruption is a normative concept of growing importance that embodies the systemic dependencies and informal practices that distort an institution’s societal mission. An extensive range of studies and lawsuits already documents strategies by which pharmaceutical companies hide, ignore, or mis- represent evidence about new drugs; distort the medi- cal literature; and misrepresent products to prescribing physicians.  We focus on the consequences for patients: millions of adverse reactions. After defining institutional corruption, we focus on evidence that it lies behind the epidemic of harms and the paucity of benefits.

It is our thesis that institutional corruption has occurred at three levels. First, through large-scale lobbying and political contributions, the pharmaceutical industry has influenced Congress to pass legislation that has compromised the mission of the Food and Drug Administration (FDA). Second, largely as a result of industry pressure, Congress has underfunded FDA enforcement capacities since 1906, and turning to industry-paid “user fees” since 1992 has biased funding to limit the FDA’s ability to protect the public from serious adverse reactions to drugs that have few offsetting advantages. Finally, industry has commercialized the role of physicians and undermined their position as independent, trusted advisers to patients." (my bold)

The authors observe that the major patent-based research pharmaceutical companies "commit" themselves to improving health at the same time as they prioritize the importance of providing their investors with a high rate of return on their stock investments.  That said, this research by Light et al shows that it is quite clear that many of these same companies are developing drugs that are little improved over their existing product lines and that these "new products" have significantly increased probablilities of adverse reactions.  Through their trade association, the Pharmaceutical Research Manufacturers of America, aka PhRMA, Big Pharma constantly remind sthe public and politicians of the high cost of research and development of new drugs, leading Congress to authorize programs that contribute billions of dollars of taxpayers money to support research and development and exempt Big Pharma from market competition through the expanding use of patent protections.  In fact, data from the National Science Foundation indicates that these "innovative" pharmaceutical companies only devote 1.3 percent of revenues after taxpayer subsidies to discovering new drugs, devoting twice as much to promotion as they do to research and development. 

Big Pharma measures its innovation in terms of new molecular entities (NMEs) but the authors' research shows that many of these NMEs provide little in terms of clinical advantages to patients and may be inferior to previously approved drugs, however they still get approval by the FDA.  Going back to the years between 1970 and the mid-1990s, research has shown that only 11 to 15.6 percent of NMEs provided important gains to patients.  In fact, as shown on this table, the therapeutic value of most 946 drugs marketed in France between 2002 and 2011, only 0.2 percent or 2 drugs provided a major breakthrough in a new area of treatment, 1.4 percent provided a significant clinical advance, and 15.6 percent resulted in more risk of harm than benefit:

By way of comparison, in the years between 1981 and 2001, the independent French drug bulletin La revue Prescrire found that 12 percent of new drugs offered therapeutic advantages over their precursors, a level that fell to 8 percent between 2002 and 2011.

By marketing drugs that are similar molecularly to their pre-existing counterparts, drug companies take on far less risk, marketing these drugs based on their newness rather than their efficacy.  Big Pharma certainly never mentions the fact that 15.6 percent of their products lead to more harm than good.  In fact, a study by J. Lexchin reveals that one in five (19.4 percent) NMEs that received approval by the FDA ends up causing serious enough harm to patients that they are either withdrawn from the marketplace or are given out to patients with a severe warning.  Of the drugs that are reviewed in less time, one in three caused serious harm.

What are the root causes of this issue?  There are three main features of the modern drug-testing system that work in the favour of industry profits and against the development of safe drugs that improve human health:

1.) The testing criteria used by the FDA contribute to the massive number of new drugs that are approved that have no increased benefits to users.  First, these drugs are tested against placebos rather than established effective drugs.  Second, the use of non-inferiority trials show only that a drug is not worse than another drug used to treat a similar symptom by more than a specific margin. 

2.) Drug companies are allowed to test their own products.  This allows them to design trials that minimize the detection of harmful side effects and maximize the benefits.  As well, drug companies are allowed to exclude patients that are most likely to have adverse reactions to their drugs; this allows them to "hand-pick" those that are most likely to benefit, making the drugs look safer and more effective than they really are.

3.) Drug companies treat trials as marketing vehicles.  Trials are designed to product results that support the marketing of a new drug.  This is followed by the hiring of statisticians and writers who produced articles for various medical journals that are favourable to the new drug.  Statistics show that drug trials that are funded by drug companies are at least 2.5 times more likely to favour the sponsor's drug in articles than those drugs that go through clinical trials that are non-commercially funded. 

As I noted in the introduction, the pharmaceutical industry pays a "user fee" under the Prescription Drug User Fee Act which was passed into law in 1992.  As I noted, this fee guarantees that drug companies will get expedited approval of the drugs that they have submitted for FDA approval.  Unfortunately, these shortened times have been good for one thing; drug companies and their profits.  An in-depth analysis found that each 10 month reduction in approval time resulted in an 18.1 percent increase in serious adverse reactions, a 10.9 precent increase in hospitalizations and a 7.2 percent increase in deaths related to drug usage

How can these issues be fixed?  The authors have five recommendations:

1.) Prevent pharmaceutical companies from testing their own drugs.  New drugs should be tested by independent institutions.

2,) New leadership is required at the FDA to build a culture focused on safety for consumers.

3.) User fees paid by Big Pharma under the current scheme must end.

4.) New drugs should require patient-relevant evidence of superiority and the number of drugs in the same class should be limited.

5.) A new National Drug Safety Board should be established to independently investigate and report on drug safety issues.

As shown on this table and graph, with the massive amount of money that Big Pharma spends on Congress annually...

...it is highly unlikely that we will see any improvement in drug efficacy and safety any time soon.

1 comment:

  1. John LeCarre's The Constant Gardener in real life. You are right. Nothing will get fixed with the amount of money going into the system to make sure it does not.